Cell-mediated immunity has been shown to be critical in controlling viral infections. Efforts to develop an effective vaccine against human immunodeficiency virus (HIV), the etiological agent of acquired immunodeficiency syndrome (AIDS), have emphasized HIV structural components such as purified native subunits, viral proteins expressed by recombinant DNA technology and synthetic peptides. These approaches, while capable of eliciting a long lasting humoral antibody response, have not been documented to induce a sustained cell-mediated immunity, and have thus far been unsuccessful. While chimpanzees are the only animals infectable with HIV, they do not develop the clinical symptoms associated with AIDS and thus may not represent a suitable animal model for AIDS vaccine trials. On the other hand, rhesus monkeys infected with simian immunodeficiency virus (SIV), a close relative of HIV, exhibit immunological and clinical manifestations similar to those observed in AIDS. We propose to clone cytotoxic T-lymphocytes (CTL) from SIV- infected rhesus macaques. Monoclonal anti-clonotypic antibodies will be generated against CTL effective in killing SIV-infected cells. The ability of the anti-clonotypic antibodies in inducing in vitro and in vivo clonal expansions of CTLs will be assessed. Their potential in preventing SIV infection and in influencing the progression of the disease in rhesus monkeys will be examined. It is anticipated that because of the similarity between SIV and HIV, information gained from this proposal will be applicable to HIV as well.
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